OR32-5 Associations between Circulation Lipocalin 2, Body Composition, and Glucose Metabolism in Active Acromegaly

Abstract

Objective: Patients with active acromegaly display a range of abnormalities in glucose metabolism and increased bone turnover. Lipocalin 2 (Lcn2) is newly identified as a bone-derived hormone with metabolic regulatory effects. To elucidate interactions between bone and energy homeostasis in active acromegaly patients, we sought to determine whether these patients were characterized by alterations in circulating levels of Lcn2, and potential interactions with body composition and glucose metabolism. Methods: Bone-derived hormone Lcn2 (by ELISA), osteocalcin (by immunoanalysis), body composition (by dual-energy x-ray absorptiometry), and glucose metabolism [homeostasis model assessment, early-phase insulin release (InsAUC30/GluAUC30) and InsAUC120/GluAUC120] were evaluated in 54 acromegalic patients (21 males and 33 females) and in 31 age-, gender-, and body mass index-matched healthy controls (14 males and 17 females). Acromegalic patients were classified as low- or high-Lcn2 group according to the median of Lcn2 level. Results: 1) Acromegalic patients had lower Lcn2 (32.25±11.77 ng/ml vs 58.38±29.66 ng/ml, P < 0.01), higher bone formation markers (osteocalcin and total P1NP, P < 0.05 and P < 0.01, respectively), and higher bone resorption markers (β-Crosslaps, P < 0.001) than controls. After pituitary surgery, serum levels of Lcn2 increased significantly (42.40±16.20 ng/ml vs 33.39±13.45 ng/ml,P<0.01) accompanied with decreased GH and IGF-1 levels. 2) Acromegalic patients had more lean body mass (P < 0.05), less total and trunk fat mass (P < 0.05) than controls. Positive correlation was found for Lcn2 and total or trunk lean mass (r = 0.457, 0.444, P < 0.01). No correlation was observed with Lcn2 and total or trunk fat mass. 3)Lcn2 was not correlated with fasting blood glucose or HbA1c. Compared to low-Lcn2 group, acromegalic patients in high-Lcn2 group had lower HOMA-β (105.23±63.52 vs 190.60±150.83, P < 0.05). Early-phase insulin release (InsAUC30/GluAUC30) and InsAUC120/GluAUC120 were also decreased in high-Lcn2 group (P < 0.01). No difference was found in HOMA-IR between low- and high-Lcn2 group. Conclusion: These data confirm and establish novel and complex interactions between bone, energy metabolism, and β cell function and suggest an unfavorable effect of Lcn2 and GH/IGF-I in combination.